期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 103, 期 7, 页码 2380-2385出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0506668103
关键词
integrin; fibronectin; fibronectin binding protein; tonsils
资金
- NIAID NIH HHS [R01 AI034503, AI34503] Funding Source: Medline
Group A Streptococcus (GAS) and other bacterial pathogens are known to interact with integrins as an initial step in a complex pathway of bacterial ingestion by host cells. Efficient GAS invasion depends on the interaction of bound fibronectin (Fn)with integrins and activation of integrin signaling. TGF-beta 1 regulates expression of integrins, Fn, and other extracellular matrix proteins, and positively controls the integrin signaling pathway. Therefore, we postulated that TGF-beta 1 levels could influence streptococcal invasion of mammalian cells. Pretreatment of HEp-2 cells with TGF-beta 1 increased their capacity to ingest GAS when the bacteria expressed fibronectin-binding proteins (M1 or PrtF1). Western blots revealed significant induction of alpha 5 integrin and Fn expression by HEp-2 cells in response to TGF-beta 1. Increased ingestion of streptococci by these cells was blocked by a specific inhibitor of the TGF-beta 1 receptor I and antibodies directed against a5 integrin and Fn, indicating that increased invasion depends on TGF-beta 1 up-regulation of both the a5 integrin and Fn. The capacity of TGF-beta 1 to up-regulate integrin expression and intracellular invasion by GAS was reproduced in primary human tonsil fibroblasts, which could be a source of TGF-beta 1 in chronically infected tonsils. The relationship between TGF-beta 1 and GAS invasion was strengthened by the observation that TGF-beta 1 production was stimulated in GAS-infected primary human tonsil fibroblasts. These findings suggest a mechanism by which GAS induce a cascade of changes in mammalian tissue leading to elevated expression of the alpha 5 beta 1 receptor, enhanced invasion, and increased opportunity for survival and persistence in their human host.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据